Study: Minor Memory Problems Merit Attention

'Senior moments' predict serious cognitive deficits years down the line.

Discussant: Ernestine Wright, MD Please click the bottom right corner for full screen.

by John Gever John Gever Managing Editor, MedPage Today
September 24, 2014

Action Points

Patients who report memory complaints are at a higher risk of future cognitive impairment.

Patients with reported memory complaints who were smokers took less time to transition to mild cognitive impairment, while hormone-replaced women took longer to transition directly to dementia.

Patients who reported having lost a step mentally were at nearly triple the risk of being diagnosed with definite cognitive impairment later on, albeit with a lag of about 6 to 10 years, researchers said.

Among participants in the prospective "BRAiNS" cohort study, those who complained of recent memory problems had a significantly higher risk of receiving a subsequent diagnosis of mild cognitive impairment or dementia (odds ratio 2.8 versus death during follow-up, 95% CI 1.9-4.2), according to Richard J. Kryscio, PhD, of the University of Kentucky in Lexington, and colleagues.

But such transitions usually were not quick. The mean lag between the first "subjective memory complaint" and a clinical diagnosis was 9.2 years for mild cognitive impairment (95% CI 7.3-11.2) and 6.1 years for those transitioning directly to dementia (95% CI 4.5-7.7), the researchers reported online in Neurology. (Some results from the study were also reported last year at the Alzheimer's Association International Conference.)

Certain other factors made the risk of mild cognitive impairment or dementia following a subjective complaint even greater, and/or shortened the time to receive a diagnosis. These included an APOE4 genotype and a history of smoking which shortened the time to diagnosis while for HRT users, the transition from memory complaints directly to dementia was lengthened by 9.7 years.

"The present study adds strong evidence to the literature supporting the hypothesis that subjective memory complaints are common among older adults and are often prognostic of future cognitive impairment," Kryscio and colleagues wrote. "Physicians should solicit and monitor [such complaints] from their older patients."

They added that the long lag seen in the study meant that subjective complaints "are not a cause for immediate alarm."

Ernestine Wright, MD, of Mercy Medical Center in Baltimore, who was not involved in the study, told MedPage Today that this window gives patients and their physicians an opportunity to try to delay onset of more severe impairments.

She said clinicians can tell patients about the increased long-term risk and use this as a means to encourage patients to adopt healthier lifestyles.

"We now know, based on this study, that perhaps those [subjective complaints] are symptoms and signs we should not ignore," Wright said. Consequently, she added, patients can be told, "These are the things you can do: you can start exercising your brain by perhaps learning something new, keeping yourself healthy in terms of exercising regularly, socializing more, and focusing on eating the right foods that we know can help with brain function."

Wright said the study should change clinical practice.

Douglas Scharre, MD, of Ohio State University's Memory Disorders Research Center, told MedPage Today in an email that the study highlights the importance of regular cognitive screening for adults who complain of memory problems.

"The advice [for those with subjective complaints] is to get baseline cognitive testing, check for mood issues, perhaps check thyroid and B12 levels, and then return yearly for repeat cognitive screening," said Scharre, who also was not involved with the study.

The clinical significance of subjective memory complaints has been debated. They've sometimes been dismissed as simply normal aging, but some studies have shown that they do presage more significant impairments.

However, Kryscio and colleagues noted, most earlier studies had only addressed transitions to full-blown dementia and had examined a relatively narrow range of other risk factors that might speed such transitions.

The current study involved 531 members of the ongoing BRAiNS cohort study, which has been following a large group of initially healthy individuals who enrolled at age 60 or older and who agreed to donate their brains for postmortem analysis.

Mean age at enrollment was 73 (SD 7). The cohort was relatively well educated, with a mean 16 years of schooling (SD 2). Some 63% of the cohort were women, and 30% were APOE4 carriers.

Participants underwent annual neurocognitive assessments, at which they were asked if they thought they had developed memory problems since their last visit. Those answering "yes" who didn't qualify for a formal diagnosis of mild cognitive impairment or dementia -- 296 during the course of the study thus far -- were classed as having subjective memory complaints.

Of these 296, 72 subsequently progressed to mild cognitive impairment, 42 to dementia, and 127 died. (The researchers did not allow patients to have a diagnosis reversed -- there were 19 diagnosed at some point with mild cognitive impairment who subsequently appeared cognitively normal, but these were recorded post hoc "so that all transitions flow[ed] consistently from less impaired to more impaired.")

The other 235 patients either remained cognitively normal (130), died without reclassification (62), or progressed directly to dementia (10) or mild impairment (33).

Kryscio and colleagues noted that large majorities of those eventually diagnosed with mild impairment or dementia (67% and 80%, respectively) had first reported subjective memory problems.

In the researchers' statistical analyses, patients who died without reporting or being diagnosed with cognitive problems served as the reference group. This led to some surprising-seeming relative risks, such as diabetes and current smoking being associated with reduced risk of developing subjective or diagnosed cognitive deficits during the study -- which occurred, the investigators explained, "because these risk factors promote mortality."

Just under half of the cohort (243) had died and underwent brain autopsies, allowing the occurrence of subjective memory complaints and clinical diagnoses to be checked against subsequent brain pathologies. Mean neuritic plaque counts increased progressively with each step in the researchers' classification scheme, both in the medial temporal region and in the neocortex. This was also the case with neurofibrillary tangle counts in the neocortex, but less so in the medial temporal region.

Kryscio and colleagues cited a number of limitations in the study. Subjective memory complaints were elicited with a single question each year and no further investigation, such as checking with family members, was conducted. Depressive symptoms that did not meet criteria for major depression -- but which are known to associate with memory deficits -- were not assessed in the study either.

Also, participants had volunteered proactively and were not necessarily representative of the population at large. Kryscio and colleagues noted as well that many risk factors such as smoking status and diabetes were recorded only at baseline and were not revisited during follow-up.

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